Comparison of the Influence of Bisphenol A and Bisphenol S on the Enteric Nervous System of the Mouse Jejunum.

Bisphenols are dangerous endocrine disruptors that pollute the environment. Due to their chemical properties, they are globally used to produce plastics. Structural similarities to oestrogen allow bisphenols to bind to oestrogen receptors and affect internal body systems. Most commonly used in the plastic industry is bisphenol A (BPA), which also has negative effects on the nervous, immune, endocrine, and cardiovascular systems. A popular analogue of BPA-bisphenol S (BPS) also seems to have harmful effects similar to BPA on living organisms. Therefore, with the use of double immunofluorescence labelling, this study aimed to compare the effect of BPA and BPS on the enteric nervous system (ENS) in mouse jejunum. The study showed that both studied toxins impact the number of nerve cells immunoreactive to substance P (SP), galanin (GAL), vasoactive intestinal polypeptide (VIP), the neuronal isoform of nitric oxide synthase (nNOS), and vesicular acetylcholine transporter (VAChT). The observed changes were similar in the case of both tested bisphenols. However, the influence of BPA showed stronger changes in neurochemical coding. The results also showed that long-term exposure to BPS significantly affects the ENS.

An evaluation of dogs' exposure to benzophenones through hair sample analysis.

Introduction: Benzophenones (BPs) are used in various branches of industry as ultraviolet radiation filters, but they pollute the natural environment, penetrate living organisms, and disrupt endocrine balance. Knowledge of the exposure of domestic animals to these substances is extremely scant. The aim of the study was to investigate long-term exposure of companion dogs to BPs and relate this to environmental factors. Material and Methods: Hair samples taken from 50 dogs and 50 bitches from under 2 to over 10 years old were analysed for BP content with liquid chromatography-tandem mass spectrometry. Results: The results revealed that dogs are most often exposed to 2-hydroxy-4-methoxybenzophenone (BP-3) and 4-dihydroxybenzophenone (BP-1). Concentration levels of BP-3 above the method quantification limit (MQL) were noted in 100% of the samples and fluctuated from 4.75 ng/g to 1,765 ng/g. In turn, concentration levels of BP-1 above the MQL were noted in 37% of the samples and ranged from <0.50 ng/g to 666 ng/g. Various factors (such as the use of hygiene and care products and the dog's diet) were found to affect BP concentration levels. Higher levels of BP-3 were observed in castrated/spayed animals and in animals that required veterinary intervention more often. Conclusion: The results obtained show that the analysis of hair samples may be a useful matrix for biomonitoring BPs in dogs, and that these substances may be toxic to them.

Exposure assessment of dairy cows to parabens using hair samples analysis.

Parabens (PBs) are used as preservatives in various products. They pollute the environment and penetrate living organisms, showing endocrine disrupting activity. Till now studies on long-term exposure of farm animals to PBs have not been performed. Among matrices using in PBs biomonitoring hair samples are becoming more and more important. During this study concentration levels of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) butyl paraben (BuP) and benzyl paraben (BeP) were evaluated using liquid chromatography-mass spectrometry (LC-MS) in hair samples collected from dairy cows bred in the Kyrgyz Republic. MeP was noted in 93.8% of samples (with mean concentration levels 62.2 ± 61.8 pg/mg), PrP in 16.7% of samples (12.4 ± 6.5 pg/mg) and EtP in 8.3% of samples (21.4 ± 11.9 pg/mg). BuP was found only in one sample (2.1%) and BeP was not detected in any sample included in the study. Some differences in MeP concentration levels in the hair samples depending on district, where cows were bred were noted. This study has shown that among PBs, dairy cows are exposed mainly to MeP, and hair samples may be a suitable matrix for research on PBs levels in farm animals.

Biomonitoring of benzophenones in guano samples of wild bats in Poland.

Benzophenones (BPs) are substances used in the production of sunscreens, cosmetics, and personal care products. However, there is a lack of knowledge of BPs in wild animals. Therefore, the study aimed to assess the concentration of selected BPs commonly used in the cosmetic industry in guano samples collected from 4 colonies of greater mouse-eared bats (Myotis myotis). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to determine guano concentrations of benzophenone 1 (BP-1), benzophenone 2 (BP-2), benzophenone 3 (BP-3) and benzophenone 8 (BP-8). BP-1 levels above the method quantification limit (MQL) were noted in 97.5% of samples and fluctuated from <0.1 ng/g to 259 ng/g (mean 41.50 ng/g, median 34.8). The second most common was BP-3, which fluctuated from <0.1 ng/g to 19 ng/g (mean 6.67 ng/g, median 5.05), and its levels higher than MQL were observed in 40% of samples. BP-2 and BP-8 concentrations did not exceed the method detection limit (0.04 ng/g) in any analyzed sample. There were visible differences in the BP-1 and BP-3 levels among the studied bat colonies. Mean BP-1 concentration fluctuated from 11.23±13.13 ng/g to 76.71±65.51 ng/g and differed significantly between the colonies. Mean BP-3 concentration fluctuated from 5.03±6.03 ng/g to 9.18±7.65 mg/g, but it did not differ significantly between the colonies. The results show that guano is a suitable matrix for the assessment of wildlife exposure to BPs. This could be particularly advantageous in protected species, where not disturbing and stressing the animals are crucial.

Poly- and perfluoroalkyl substances (PFASs) in amphibians and reptiles - exposure and health effects.

Poly- and perfluoroalkyl substances (PFASs) are commonly used in various industries and everyday products, including clothing, electronics, furniture, paints, and many others. PFASs are primarily found in aquatic environments, but also present in soil, air and plants, making them one of the most important and dangerous pollutants of the natural environment. PFASs bioaccumulate in living organisms and are especially dangerous to aquatic and semi-aquatic animals. As endocrine disruptors, PFASs affect many internal organs and systems, including reproductive, endocrine, nervous, cardiovascular, and immune systems. This manuscript represents the first comprehensive review exclusively focusing on PFASs in amphibians and reptiles. Both groups of animals are highly vulnerable to PFASs in the natural habitats. Amphibians and reptiles, renowned for their sensitivity to environmental changes, are often used as crucial bioindicators to monitor ecosystem health and environmental pollution levels. Furthermore, the decline in amphibian and reptile populations worldwide may be related to increasing environmental pollution. Therefore, studies investigating the exposure of amphibians and reptiles to PFASs, as well as their impacts on these organisms are essential in modern toxicology. Summarizing the current knowledge on PFASs in amphibians and reptiles in a single manuscript will facilitate the exploration of new research topics in this field. Such a comprehensive review will aid researchers in understanding the implications of PFASs exposure on amphibians and reptiles, guiding future investigations to mitigate their adverse effects of these vital components of ecosystems.

Neuregulin 1 (NRG1) and its receptors in the enteric nervous system and other parts of the gastrointestinal wall.

Neuregulin 1 (NRG1) belonging to the transmembrane growth factors family is widespread in living organisms. It acts through ErbB family receptors and first of all takes part in embryogenesis, as well as in developmental, regenerative and adaptive processes occurring in various internal organs and systems. It is known that NRG1 and its receptors are present in various parts of the gastrointestinal (GI) tract. First of all NRG1 and ErbB receptors have been detected in the enteric nervous system (ENS) localized in the wall of the esophagus, stomach and intestine and regulating the majority of the GI tract functions, but also in the mucosal and muscular layers of the GI tract. The NRG1/ErbB pathway is involved in the development and differentiation of the ENS and regulation of the intestinal epithelium functions. Moreover, dysregulation of this pathway results in a wide range of gastrointestinal diseases. However, till now there are no summarizations of previous studies concerning distribution and functions of NRG1 and its receptors in the GI tract. The present review fills this gap.

Biomonitoring of parabens in wild boars through hair samples analysis.

Parabens are compounds widely utilized in the industry as preservative additives to personal care products, cosmetics and food. They pollute the environment and penetrate to the living organisms through the digestive tract, respiratory system and skin. Till now the knowledge about exposure of terrestrial wild mammals to parabens is extremely scarce. Therefore, this study for the first time assessed the concentration levels of five parabens commonly used in industry (methylparaben-MeP, ethylparaben-EtP propylparaben-PrP, benzylparaben -BeP and butylparaben-BuP). Substances have been analyzed in hair samples collected from wild boars using liquid chromatography-mass spectrometry (LC-MS) method. The hair is a matrix, which allows to study long-term exposure of organisms to parabens. During this study MeP was noted in 96.3% of samples with mean 88.3±72.9 pg/mg, PrP in 87.0% of samples with mean 8.5±3.3 pg/mg, BeP in 44.4% of samples with mean 17.2±12.3 pg/mg and EtP in 11.1% of samples with mean 17.2±4.8 pg/mg. In turn BuP was noted only in 3.7% of samples with concentration levels below limit of quantification (2.6 pg/mg). Statistically significant intragender differences in parabens levels have not been noted. Only BeP concentration levels depended on industrialization and density of human population of area, where the animals lived. This study indicates that wild boars are exposed to parabens, especially to MeP and PrP, and analysis of the hair seems to be a useful tool of biomonitoring of parabens in wild mammals.

A comprehensive transcriptomic analysis of the bisphenol A affected kidney in mice.

Introduction: Bisphenol A (BPA) is a substance belonging to the endocrine-disrupting chemicals, globally used in the production of polycarbonate plastics. It has been found that BPA enhances carcinogenesis, triggers obesity and exerts a pathogenic effect in several disorders, such as type 2 diabetes, asthma, or increased blood pressure. Recent studies have revealed, that BPA has a harmful impact on the kidneys function, therefore, the current research aimed to explore the specific molecular changes triggered in these organs after oral BPA exposure in mice. Materials and Methods: The experiment was carried out on 12 (3-month-old) female mice. Six mice served as controls. The other 6 mice were treated with BPA in the drinking water at a dose of 50 mg/kg b. w. for 3 months. Then animals were euthanized, the kidneys were collected, and extracted RNA was used to perform RNA-seq. Results: Applied multistep bioinformatics revealed 433 differentially expressed genes (DEGs) in the BPA-treated kidneys (232 upregulated and 201 downregulated). Additionally, 95 differentially expressed long-noncoding RNAs (DELs) were revealed in BPA samples. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations indicated that BPA exposure resulted in profound changes in several essential processes, such as oxidative phosphorylation, mitochondrial and ribosome function, or chemical carcinogenesis. Conclusion: The obtained novel results suggest that BPA has a harmful impact on the fundamental processes of the kidney and significantly impairs its function by inducing mitochondrial dysfunction leading to oxidative stress and reactive oxygen species production.

Bisphenol A Effects on Neurons' Neurochemical Character in the Urinary Bladder Intramural Ganglia of Domestic Pigs.

Bisphenol A (BPA), a substance globally used to produce plastics, is part of many everyday items, including bottles, food containers, electronic elements, and others. It may penetrate the environment and living organisms, negatively affecting, among others, the nervous, immune, endocrine, and cardiovascular systems. Knowledge of the impact of BPA on the urinary bladder is extremely scarce. This study investigated the influence of two doses of BPA (0.05 mg/kg body weight (b.w.)/day and 0.5 mg/kg b.w./day) given orally for 28 days on the neurons situated in the ganglia located in the urinary bladder trigone using the typical double immunofluorescence method. In the study, an increase in the percentage of neurons containing substance P (SP), galanin (GAL), a neuronal isoform of nitric oxide synthase (nNOS-used as the marker of nitrergic neurons), and/or cocaine- and amphetamine-regulated transcript (CART) peptide was noted after BPA administration. The severity of these changes depended on the dose of BPA and the type of neuronal factors studied. The most visible changes were noted in the cases of SP- and/or GAL-positive neurons after administering a higher dose of BPA. The results have shown that oral exposure to BPA, lasting even for a short time, affects the intramural neurons in the urinary bladder wall, and changes in the neurochemical characterisation of these neurons may be the first signs of BPA-induced pathological processes in this organ.

Assessment of perfluoroalkyl substances concentration levels in wild bat guano samples.

Perfluoroalkyl substances (PFASs) are substances commonly used in the production of various everyday objects, including among others kitchen dishes, cosmetics, or clothes. They penetrate to the environment and living organisms causing disturbances in the functioning of many internal organs and systems. Due to environmental pollution, wildlife is also exposed to PFASs, but the knowledge about this issue is rather limited. The aim of this study was to evaluate the exposure of wild greater mouse-eared bats (Myotis myotis), living in Poland, to six selected PFASs: five perfluoroalkyl carboxylic acids (perfluorobutanoic acid-PFBuA, perfluoropentanoic acid-PFPeA, perfluorohexanoic acid-PFHxA, perfluoroheptanoic acid-PFHpA, perfluorooctanoic acid-PFOA) and perfluorooctane sulfonic acid (PFOS) through the analysis of guano samples with liquid chromatography with tandem mass spectrometry (LC-MS-MS) method. To our knowledge this is the first study concerning the PFASs levels in bats, as well as using guano samples to evaluate the exposure of wild mammals to these substances. A total of 40 guano samples were collected from 4 bats summer (nursery) colonies located in various parts of Poland. The presence of PFASs mentioned were detected in all colonies studied, and concentration levels of these substances were sampling dependent. The highest concentration levels were observed in the case of PFPeA [1.34 and 3060 ng/g dry weight (dw)] and PFHxA (8.30-314 ng/g dw). This study confirms the exposure of wild bats to PFASs.

The Carcinogenic Potential of Bisphenol A in the Liver Based on Transcriptomic Studies.

Bisphenol A (BPA) is an environmental toxin widely used in the production of polycarbonate plastics. A correlation exists between BPA tissue contamination and the occurrence of pathological conditions, including cancer. First-passage detoxification of high BPA amounts in the liver promotes hepatotoxicity and morphological alterations of this organ, but there is a lack of knowledge about the molecular mechanisms underlying these phenomena. This prompted us to investigate changes in the liver transcriptomics of 3-month-old female mice exposed to BPA (50 mg/kg) in drinking water for 3 months. Five female mice served as controls. The animals were euthanized, the livers were collected, and RNA was extracted to perform RNA-seq analysis. The multistep transcriptomic bioinformatics revealed 120 differentially expressed genes (DEGs) in the BPA-exposed samples. Gene Ontology (GO) annotations indicated that DEGs have been assigned to many biological processes, including "macromolecule modification" and "protein metabolic process". Several of the revealed DEGs have been linked to the pathogenesis of severe metabolic liver disorders and malignant tumors, in particular hepatocellular carcinoma. Data from this study suggest that BPA has a significant impact on gene expression in the liver, which is predictive of the carcinogenic potential of this compound in this organ.

Influence of bisphenol A and its analog bisphenol S on cocaine- and amphetamine-regulated transcript peptide-positive enteric neurons in the mouse gastrointestinal tract.

Introduction: Bisphenol A (BPA) is used in large quantities for the production of plastics and is present in various everyday objects. It penetrates living organisms and shows multidirectional adverse influence on many internal organs. For this reason, BPA is often replaced in plastic production by other substances. One of them is bisphenol S (BPS), whose effects on the enteric nervous system (ENS) have not been explained. Methods: Therefore, the present study compares the influence of BPA and BPS on the number of enteric neurons immunoreactive to cocaine-and amphetamine-regulated transcript (CART) peptide located in the ENS of the stomach, jejunum and colon with the use of double immunofluorescence method. Results: The obtained results have shown that both bisphenols studied induced an increase in the number of CART-positive enteric neurons, and the severity of changes depended on the type of enteric ganglion, the dose of bisphenols and the segment of the digestive tract. The most visible changes were noted in the myenteric ganglia in the colon. Moreover, in the colon, the changes submitted by BPS are more noticeable than those observed after BPA administration. In the stomach and jejunum, bisphenol-induced changes were less visible, and changes caused by BPS were similar or less pronounced than those noted under the impact of BPA, depending on the segment of the gastrointestinal tract and ganglion type studied. Discussion: The results show that BPS affects the enteric neurons containing CART in a similar way to BPA, and the BPS impact is even stronger in the colon. Therefore, BPS is not neutral for the gastrointestinal tract and ENS.

Exposure assessment to bisphenol A (BPA) and its analogues bisphenol S (BPS) and bisphenol F (BPF) in wild boars by hair analysis.

Bisphenols are widely used in various branches of industry for the production of plastics. They penetrate to the natural environment and thus living organisms. As endocrine disruptors, bisphenols have adverse effects on various internal organs and systems. Contrary to humans, the knowledge of the exposure of wild terrestrial mammals to bisphenols is extremely limited. Therefore, this study for the first time assessed the exposure level of wild boars to three bisphenols commonly used in industry (i.e. bisphenol A - BPA, bisphenol S - BPS and bisphenol F - BPF) using hair sample analysis in liquid chromatography-mass spectrometry (LC-MS). The presence of BPA and/or BPS has been noted in the samples collected from >80 % of animals included in the study (n = 54), while the presence of BPF was not found in any sample. At least one of the bisphenols was present in every sample tested. Mean concentrations of BPA and BPS in the hair of wild boars were 151.40 ± 135.10 pg/mg dry weight (dw.) and 29.40 ± 36.97 pg./mg dw, respectively. Concentrations of BPA and BPS in females were statistically higher than in males (p < 0.05). Moreover, statistically significantly higher concentration levels of BPA (and not BPS) in the areas with higher degree of industrialization and higher human population density were also found. This is the first study concerning the use of hair samples to assess the exposure of wild terrestrial mammals to bisphenols. The obtained results show that an analysis of the hair may be a useful tool of biomonitoring bisphenols in wild animals. The presence of BPA and BPS in wild boar hair in relatively high concentration also suggests that these substances may have an influence on the health status not only in humans and aquatic animals, but also in wild terrestrial mammals. However, many aspects connected with this issue are not clear and require further study.

Changes Caused by Bisphenols in the Chemical Coding of Neurons of the Enteric Nervous System of Mouse Stomach.

Bisphenol A (BPA), an organic chemical compound which is widely used in the production of plastics, can severely damage live organisms. Due to these findings, the plastic industry has started to replace it with other substances, most often with bisphenol S (BPS). Therefore, during the present investigation, with the use of double immunofluorescence labeling, we compared the effect of BPA and BPS on the enteric nervous system (ENS) in the mouse corpus of the stomach. The obtained results show that both studied toxins impact the amount of nerve cells immunoreactive to substance P (SP), galanin (GAL), vesicular acetylcholine transporter (VAChT is used here as a marker of cholinergic neurons) and vasoactive intestinal polypeptide (VIP). Changes observed under the impact of both bisphenols depended on the neuronal factor, the type of the enteric ganglion and the doses of bisphenols studied. Generally, the increase in the percentage of neurons immunoreactive to SP, GAL and/or VIP, and the decrease in the percentage of VAChT-positive neurons, was noted. Severity of changes was more visible after BPA administration. However, the study has shown that long time exposure to BPS also significantly affects the ENS.

Evaluation of Parabens and Bisphenol A Concentration Levels in Wild Bat Guano Samples.

Parabens and bisphenol A are synthetic compounds found in many everyday objects, including bottles, food containers, personal care products, cosmetics and medicines. These substances may penetrate the environment and living organisms, on which they have a negative impact. Till now, numerous studies have described parabens and BPA in humans, but knowledge about terrestrial wild mammals' exposure to these compounds is very limited. Therefore, during this study, the most common concentration levels of BPA and parabens were selected (such as methyl paraben-MeP, ethyl paraben-EtP, propyl paraben-PrP and butyl paraben-BuP) and analyzed in guano samples collected in summer (nursery) colonies of greater mouse-eared bats (Myotis myotis) using liquid chromatography with the tandem mass spectrometry (LC-MS-MS) method. MeP has been found in all guano samples and its median concentration levels amounted to 39.6 ng/g. Other parabens were present in smaller number of samples (from 5% for BuP to 62.5% for EtP) and in lower concentrations. Median concentration levels of these substances achieved 0.95 ng/g, 1.45 ng/g and 15.56 ng/g for EtP, PrP and BuP, respectively. BPA concentration levels did not exceed the method quantification limit (5 ng/g dw) in any sample. The present study has shown that wild bats are exposed to parabens and BPA, and guano samples are a suitable matrix for studies on wild animal exposure to these substances.

Effects of the long-term influence of bisphenol A and bisphenol S on the population of nitrergic neurons in the enteric nervous system of the mouse stomach.

Bisphenol A (BPA) is an endocrine disruptor commonly used in the production of plastics. Due to its relatively well-known harmful effects on living organisms, BPA is often replaced by its various analogues. One of them is bisphenol S (BPS), widely used in the plastics industry. Until recently, BPS was considered completely safe, but currently, it is known that it is not safe for various internal organs. However, knowledge about the influence of BPS on the nervous system is scarce. Therefore, the aim of this study was to investigate the influence of two doses of BPA and BPS on the enteric nitrergic neurons in the CD1 strain mouse stomach using the double-immunofluorescence technique. The study found that both substances studied increased the number of nitrergic neurons, although changes under the impact of BPS were less visible than those induced by BPA. Therefore, the obtained results, for the first time, clearly indicate that BPS is not safe for the innervation of the gastrointestinal tract.

Changes in the Enteric Neurons Containing Selected Active Substances in the Porcine Descending Colon after the Administration of Bisphenol A (BPA).

Bisphenol A (BPA) is an endocrine disruptor widely distributed in the environment due to its common use in the plastics industry. It is known that it has a strong negative effect on human and animal organisms, but a lot of aspects of this impact are still unexplored. This includes the impact of BPA on the enteric nervous system (ENS) in the large intestine. Therefore, the aim of the study was to investigate the influence of various doses of BPA on the neurons located in the descending colon of the domestic pig, which due to similarities in the organization of intestinal innervation to the human gastrointestinal tract is a good animal model to study processes occurring in human ENS. During this study, the double immunofluorescence technique was used. The obtained results have shown that BPA clearly affects the neurochemical characterization of the enteric neurons located in the descending colon. The administration of BPA caused an increase in the number of enteric neurons containing substance P (SP) and vasoactive intestinal polypeptide (VIP) with a simultaneously decrease in the number of neurons positive for galanin (GAL) and vesicular acetylcholine transporter (VAChT used as a marker of cholinergic neurons). Changes were noted in all types of the enteric plexuses, i.e., the myenteric plexus, outer submucous plexus and inner submucous plexus. The intensity of changes depended on the dose of BPA and the type of enteric plexus studied. The results have shown that BPA may affect the descending colon through the changes in neurochemical characterization of the enteric neurons located in this segment of the gastrointestinal tract.